ABSTRACT
Amplification of the 11q13 region is a prevalent genetic alteration in head and neck squamous cell carcinoma (HNSCC). We investigated the clinical significance of cortactin (CTTN) and cyclin D1 (CCND1) amplification in both malignant transformation and tumour progression. CTTN and CCND1 amplification was analysed by differential and real-time PCR in a prospective series of laryngeal/pharyngeal carcinomas and archival premalignant tissues. CTTN mRNA and protein expression were respectively determined by real-time RT-PCR and immunohistochemistry, and correlated with gene status. Molecular alterations were associated with clinicopathological parameters and disease outcome. CTTN and CCND1 amplifications were respectively found in 75 (37%) and 90 (45%) tumours. Both correlated with advanced disease; however, only CTTN amplification was associated with recurrence and reduced disease-specific survival (p = 0.0022). Strikingly, CTTN amplification differentially influenced survival depending on tumour site (p = 0.0001 larynx versus p = 0.68 pharynx) and was an independent predictor of reduced survival in the larynx (p = 0.04). CCND1 amplification was detected in early tumourigenesis and increased with the severity of dysplasia. Importantly, CTTN amplification was only found in high-grade dysplasias that progressed to invasive carcinoma. CTTN gene status strongly correlated with mRNA and protein expression. Furthermore, CTTN overexpression correlated significantly with reduced disease-specific survival (p = 0.018). Taken together, these data indicate that CTTN may serve as a valuable biomarker to identify patients with laryngeal tumours at high risk of recurrence and poor outcome.
Subject(s)
Carcinoma, Squamous Cell/genetics , Chromosomes, Human, Pair 11 , Cortactin/genetics , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/genetics , Neoplasm Recurrence, Local/genetics , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cortactin/analysis , Cortactin/metabolism , Cyclin D1/analysis , Cyclin D1/genetics , Cyclin D1/metabolism , Female , Gene Amplification , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Proportional Hazards Models , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Survival RateABSTRACT
OBJECTIVE: Adenoid cystic carcinoma (ACC) is a tumour of epithelial origin that represents the most common malignant neoplasm of the minor salivary glands. However, little is known about the genes involved in the development and progression of this tumour. Cyclin D1 gene (CCND1) plays a key role in the control of the cell cycle, and its amplification is described in numerous cancers. The aim of this study is to determine the amplification of the CCND1 gene in the ACC of the minor salivary glands. MATERIALS AND METHODS: A retrospective study was performed on 12 patients with ACC of the head and neck. The amplification of the CCND1 was determined using multiple PCR. RESULTS: Amplification of the CCND1 was found in 4 patients (33.3%). No correlation was found between CCND1 amplification and clinicopathological parameters, although disease-free survival was diminished in patients with amplification. DISCUSSION/CONCLUSIONS: Our study demonstrates for the first time the amplification of the CCND1 gene in ACC. We have found an amplification rate similar to others neoplasms. CCND1 amplification seems to be associated with a poorer prognosis in these tumours, although this needs to be confirmed in larger studies.
Subject(s)
Carcinoma, Adenoid Cystic/genetics , Carcinoma, Adenoid Cystic/pathology , Cyclin D1/genetics , Gene Amplification , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/pathology , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
Introducción/Objetivo: El carcinoma adenoide quístico (CAQ) es un tumor de estirpe epitelial y representa el tumor maligno más frecuente de las glándulas salivares menores. Sin embargo, se conoce poco de los genes implicados en el desarrollo y progresión de estos tumores. El gen de la ciclina D1 (CCND1) juega un papel clave en el control del ciclo celular, y su anomalía está descrita en numerosos cánceres. El objetivo de este estudio es determinar si existe amplificación del CCND1 en los CAQ de glándulas salivares menores y su posible relación con el pronóstico. Material y métodos: Se realiza un estudio retrospectivo de 12 pacientes intervenidos de CAQ de fosas nasales y senos paranasales. Se determinó la existencia de amplificación del CCND1 mediante PCR múltiple. Resultados: Se encontró amplificación del CCND1 en 4 casos (33,3 por ciento). No se halló relación significativa con ninguno de los parámetros clínico-patológicos analizados (localización, tipo histológico, estadio; p>0,05). La supervivencia fue menor en los pacientes que presentaban amplificación de CCND1. Discusión/Conclusiones: Nuestro estudio es el primero que demuestra la amplificación del gen de la ciclina D1 en los CAQ. La amplificación del CCND1 parece tener relación con un peor pronóstico en estos tumores, aunque es necesario confirmar esta relación en estudios más amplios (AU)
OBJECTIVE: Adenoid cystic carcinoma (ACC) is a tumour of epithelial origin that represents the most common malignant neoplasm of the minor salivary glands. However, little is known about the genes involved in the development and progression of this tumour. Cyclin D1 gene (CCND1) plays a key role in the control of the cell cycle, and its amplification is described in numerous cancers. The aim of this study is to determine the amplification of the CCND1 gene in the ACC of the minor salivary glands. MATERIALS AND METHODS: A retrospective study was performed on 12 patients with ACC of the head and neck. The amplification of the CCND1 was determined using multiple PCR. RESULTS: Amplification of the CCND1 was found in 4 patients (33.3%). No correlation was found between CCND1 amplification and clinicopathological parameters, although disease-free survival was diminished in patients with amplification. DISCUSSION/CONCLUSIONS: Our study demonstrates for the first time the amplification of the CCND1 gene in ACC. We have found an amplification rate similar to others neoplasms. CCND1 amplification seems to be associated with a poorer prognosis in these tumours, although this needs to be confirmed in larger studies (AU)
Subject(s)
Middle Aged , Male , Humans , Female , Aged , Adult , Gene Amplification , Cyclin D1/genetics , Carcinoma, Adenoid Cystic/genetics , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/pathology , Carcinoma, Adenoid Cystic/pathologyABSTRACT
OBJECTIVE: Previous studies have investigated the role of viruses in tumor origin of head and neck cancer. Despite this, mechanis of viral carcinogenesis remain unclear. The aim of this study is to determine the prevalence of herpes simplex virus (HSV) and Epstein-Barr virus (EBV) in malignant laryngeal and oropharyngeal lesions. MATERIAL AND METHODS: Fresh frozen specimens of 28 laryngeal and oropharyngeal squamous cell carcinomas were studied. The presence or absence of HSV and EBV was determined with polymerase chain reaction (PCR) assays. RESULTS: None of the samples showed evidence for EBV DNA. One tonsilar carcinoma case (3.5%) was positive for HSV DNA detection. CONCLUSIONS: These results do not support HSV and EBV as etiological factors in head and neck cancer.
Subject(s)
Carcinoma, Squamous Cell/virology , Head and Neck Neoplasms/virology , Herpesvirus 4, Human/isolation & purification , Simplexvirus/isolation & purification , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
Objetivo: Diversos estudios han investigado el papel de los virus en la carcinogénesis de los tumores de cabeza y cuello. A pesar de esto, el mecanismo de la carcinogénesis viral permanece poco claro. El objetivo de este estudio es determinar la prevalencia del virus herpes simplex (VHS) y del virus de Epstein-Barr (VE-B) en tumores malignos de laringe y orofaringe. Material y método: Se estudian muestras frescas congeladas de 28 pacientes con tumores de laringe y orofaringe. La presencia o ausencia del VHS y VE-B se determinó mediante la reacción en cadena de la polimerasa (PCR). Resultados: En ninguna de las muestras detectamos el ADN del VE-B. En una muestra de carcinoma de amígdala (3,5 por ciento) detectamos el ADN del VHS. Conclusiones: Nuestros resultados no sugieren que el VHS y el VE-B tengan un papel en la etiología de los tumores de cabeza y cuello (AU)
OBJECTIVE: Previous studies have investigated the role of viruses in tumor origin of head and neck cancer. Despite this, mechanis of viral carcinogenesis remain unclear. The aim of this study is to determine the prevalence of herpes simplex virus (HSV) and Epstein-Barr virus (EBV) in malignant laryngeal and oropharyngeal lesions. MATERIAL AND METHODS: Fresh frozen specimens of 28 laryngeal and oropharyngeal squamous cell carcinomas were studied. The presence or absence of HSV and EBV was determined with polymerase chain reaction (PCR) assays. RESULTS: None of the samples showed evidence for EBV DNA. One tonsilar carcinoma case (3.5%) was positive for HSV DNA detection. CONCLUSIONS: These results do not support HSV and EBV as etiological factors in head and neck cancer (AU)
